Method of protecting the skin from ultraviolet radiation with titanic acid and esters of titanic acid

ABSTRACT

An effective ultra-violet absorber composition and process for controlling sunburn by applying to the skin a composition which comprises a hydrated, substantially transparent gel represented by the formula: WHEREIN: A. R1 and R2 are independently selected from the group consisting of hydrogen, short chain alkyl, and ligands capable of chelate formation, and B. N IS ANY INTEGER IN A DERMATOLOGICALLY ACCEPTABLE CARRIER, THE GEL BEING EMPLOYED IN AN AMOUNT EFFECTIVE TO PROTECT THE SKIN AND OTHER SURFACES FROM THE HARMFUL EFFECTS OF THE BURNING RAYS OF THE SUN.

United States Patent Madigan [54] METHOD OF PROTECTING THE SKIN FROMULTRAVIOLET RADIATION WITH TITANIC ACID AND ESTERS OF TITANIC ACID [72]Inventor: Edward J. Madigan, Denver, C010.

[73] Assignee: Cosmetics & Pharmaceuticals, Inc.,

Denver, C010.

[22] Filed: March 3, 1969 [21] Appl. No.: 803,951

[52] US. Cl. ..424/59, 260/4293, 260/429.9,

[51] Int. Cl. ..A61l 23/00 [58] Field of Search ..424/59; 260/4293,429.5

[56] References Cited UNITED STATES PATENTS 760,319 5/1904 Dreher..260/429.5

2,684,972 7/1954 Haslam ..260/429.3 X

2,824,1 l5 2/1958 Beacham et al. ...260/429.3 X

2,935,522 5/1960 Samour .......260/429.5

[451 Oct. 10,1972

Primary Examiner-Albert T. Meyers Assistant Examiner-Dale R. OreAttorney-John E. Reilly [57] ABSTRACT An effective ultra-violet absorbercomposition and process for controlling sunburn by applying to the skina composition which comprises a hydrated, substantially transparent gelrepresented by the formula:

wherein:

a. R, and R are independently selected from the group consisting ofhydrogen, short chain alkyl, and ligands capable of chelate formation,and

b. n is any integer in a dermatologically acceptable carrier, thegelbeing employed in an amount effective to protect the skin and othersurfaces from the harmful effects of the burning rays of the sun.

3 Claims, N0 Drawings METHOD OF PROTECTING THE SKIN FROM ULTRAVIOLETRADIATION WITH TITANIC ACID AND ESTERS OF TITANIC ACID ,This inventionrelates to new and useful ultraviolet absorber compounds, tocompositions containing such compounds, to a method of preparing asun-screen composition, and to methods for protecting the human skin andother surfaces against the burning effects of sunlight. Moreparticularly the invention relates to substantially transparentgelatinous compounds adapted for incorporation into cosmeticformulations, said compounds being capable of absorbing the burningwavelengths of actinic radiation.

Extensive studies have been made of ultraviolet radiation and itseffects on the human skin. It has been established that the radiationfrom about 290 to 315 N (l Nanometer being equivalent to Angstrom Units)contains a major portion of detrimental burning wave lengths, while theradiation from about 315 to 400 N promote the more desirable aestheticfeature known as tanning. The effect of the lower wavelengths on humanskin is to produce, in most instances, severe burning, blistering anddeterioration of the skin. As a result, various sun-screen compositionshave been developed to screen out or block these burning wavelengths.While tanning may have some beneficial effects in that it protects theskin from further burning where there is continued exposure to the sun,nevertheless tanning in and of itself is associated with a generaldeterioration of the skin; and although the majority of people are notseverely affected by tanning, many are extremely sensitive even to thetanning rays of the sun to the extent that exposure to these wavelengths creates serious health hazards. Included within the latter groupare those persons who suffer from various dermatological problems, blooddyscriasis, skin cancer, and sensitive skin problems. Consequently, forthose who must have protection against the burning rays as well as aportion of the shorting tanning rays of the sun, there has been a needfor a broad spectrum, non-toxic, non-carcinogenic, sun-screencomposition that will afford adequate protection to the skin, issufficiently stable to remain effective for several hours, and can bereadily applied to the skin.

it is therefore a primary object of the present invention to providerelatively transparent gelatinous compounds which possess excellentabsorption abilities for filtering out the burning wave lengths in theultraviolet spectrum.

is is another object of the present invention to provide compositionscontaining the novel compounds hereof which may be applied to the humanskin to protect it against sunburn.

It is still another object of the present invention to provide a methodof preparing an ultra-violet absorber compound for subsequentincorporation into various dermatologically acceptable carriers.

In accordance with the present invention, it has now been discoveredthat transparent and/or translucent compounds which contain directoxygen linkages to titanium possess outstanding sun-screening abilitiesto absorb the burning rays of sunlight, and particularly those wavelengths in the ultra-violet region of from about 200 N to about 400 N.Those compounds which contain direct oxygen linkages to titanium and areemployed in the compositions and processes of this invention aresubstantially transparent gels having the following general formula:

wherein R, and R are preferably hydrogen, alkyl, and

ligands capable of chelate formation, and n represents any integer.Thus, when the formula represents: (1) a condensation product oforthotitanic acid, then n may be any integer greater than 1: and (2) thechelated form, then n is l. The alkyl is preferably of the short chainvariety having between three and eight carbon atoms such as propyl,isopropyl, butyl, isobutyl, branched eight carbon atom chains, as wellas polymers and mixtures thereof. The ligands capable of chelateformation include the amino alcohol, keto alcohols, and glycols whichupon esterification form relatively stable five or six membered ringstructures with titanium. Preferred members of this latter group aretriethanolamine, octylene glycol and acetyl acetone. The compounds areprepared as transparent gels as hereinafter described, and thereafterusually dispersed in a dermatologically acceptable carrier.

It is generally accepted that titanium chemistry is a complex subjectand for this reason, the invention should not be limited to the theoryherein presented. However, it is known that orthotitanic acid, i.e.,Ti(0l-l)., hydrolyzes readily upon exposure to water to produce highermolecular weight condensation products and/or polymeric titanatesthereof.

For example, one method forming the titanate occurs when alkyl orthotitanate esters are hydrolyzed. Hydrolysis proceeds rapidly with theintermediate formation of unstable coordination complexes between theester and water thereby splitting out a molecule of alcohol according tothe following reaction:

However, since the monohydroxy ester is unstable it immediatelyundergoes further reaction and condensation to form a dimeric condensedtitanium ester, i.e., hexalkoxy titanate. Upon further hydrolysis andunder controlled temperature conditions, it is possible to obtain ahydrous polymeric ortho titanate gel of the type represented by thefollowing formula:

HO Ti (OI-I 0-], H

wherein 1: represents any integer.

Of course the rate of hydrolysis is dependent also upon the size andcomplexity of the alkyl group; the hydrolysis rate decreasing withincreasing alkyl group size. Accordingly, because of the instability ofthe lower alkyl titanates they well undergo hydrolysis. Thus, theforegoing illustrates one method of forming an ultraviolet absorber ofthis invention.

Another and more preferred method of preparing the orthotitanic acidabsorber of this invention involves hydrolyzing titanium tetrachlorideat 0C by reacting the titanium tetrachloride with ice to form gelatinousorthotitanic acid having a pH of less than about 5.0. The gel is thenfiltered and neutralized with an alkaline solution such as diluteammonium hydroxide thereby forming a colloidal white transparentsuspension. The suspension is thereafter reacidified with an organicacid, such as, citric acid to form a crystalline hydrated titaniumdioxide precipitate which is further acidified to form a solutioncontaining Ti(OH having a pH in the range of 5.0 to 9.0. The sun-screenagent prepared according to this procedure showed substantially completeabsorption of all ultraviolet wave lengths shorter than about 375nanometers as well as a gradual decreasing gradient of absorption of thehigher ultraviolet wave lengths into the lower visible spectrum.

The titanium chelates which form a part of this invention may besatisfactorily utilized as effective sunscreen agents. Since titaniumhas a balance of four and a coordination number of six, it is possibleto form chelated esters by coordinate bonding between titanium andelectron-donating atoms, such as, nitrogen and oxygen. Accordingly, uponformation of alkyl esters of titanic acid from ligands such as aminoalcohols, keto alcohols, or glycols, the hydroxyl groups of two of theligand moles replace two alkoxy groups of the ester thereby forming arelatively stable fiveor six-membered ring via electron donation fromthe polar group to titanium. These titanium chelates can be seen ashaving the following generalized formula:

wherein at is the polar group, i.e. oxygen or nitrogen, and y may be atwo or three membered carbon chain thereby resulting in an unstrainedfiveor six-membered ring. R may be hydrogen, alkyl, or another ligandgroup. Some of the commercially available chelates are triethanolaminetitanate, titanium acetyl acetonate, tetra-octylene glycol titanate andtitanium lactate. The titanium chelates are relatively stable andgenerally slow to hydrolyze, although they are soluble in variousalcohols and alcohol-water solution, or miscible with water.

The general procedure for preparing the titanium chelate sun-screenagents of this invention involves firstly, formation of the chelate asillustrated by the preferred embodiment and secondly, incorporation ofthe chelate into a suitable carrier. Specifically, the preferred chelateembodiment of the present invention involves cosmetic compositionshaving triethanolamine titanate as the ultra-violet absorbing agent. Thechelated form of triethanolamine titanate may be prepared be reacting 1mole of tetraisopropyl titanate with two moles of triethanolamine atabout 75C to give a water soluble, substantially transparent gel whereinthe che late may be presented by the following formula:

(HO amon zlfic H2011:

aID

When the compounds of this invention are to be applied to the humanskin, they may be incorporated in various carriers such ashydroalcoholic lotions, solvent oily solutions, water, water-in-oil andoil-in-water emulsions, creams and other cosmetic preparations. Dualpurpose formulations are also contemplated, for example, a combinationsun tan and insect repellant lotion. It should also be understoodthatthe invention is not to be limited to these particular formulationsbut may be incorporated in a variety of topical preparations. Ingeneral, the cosmetic formulations desirably contain between I and 50percent of the sun-screen compound, although it should be understoodthat the concentrations are not critical but depend entirely upon thesun-screen protection desired. Furthermore, since each compoundpossesses differing ultra-violet wave length absorption abilities, eachformulation should be chosen according to the desired effect.

Various embodiments of the invention will be further illustrated by therepresentative examples as set forth below wherein parts are given byweight unless otherwise indicated.

EXAMPLE 1 This example illustrates one method of forming the basicorthotitanic acid gel.

A 500 ml. beaker was placed in an ice bath and cooled at 0C. 200 g. ofpurified titanium tetrachloride, TiCL, were placed in the beaker andcooled to 0C. Thereafter, g. of ice were added and mixed with thetitanium tetrachloride until a light yellow gel having a pH of about 3.5was formed. The gel was identified as orthotitanic acid. The gel wasthen treated with a sufficient amount of ammonium hydroxide to a pH ofabout 7.0. The neutralized gel was then washed with distilled water andfiltered.

EXAMPLE 2 The gelatinous compound of Example 1 was dissolved indistilled water at a ratio of 50 parts orthotitanic acid to 50 partsdistilled water. The product was then tested for ultra-violet absorptionability. From the following tabulated results, it is evident thatsubstantially all of the burning wavelengths, as well as a major portionof the shorter tanning rays were absorbed:

This example illustrates a further procedure by which a bufferedorthotitanic acid sun-screen was obtained.

T hirty-five g. of the gel product from Example 1 were dissolved in 20g. of distilled water. The pH of the solution was brought to about 6.0through the addition of 11 g. of a 50 percent ammonium hydroxidesolution and 100 ml. of distilled water to obtain a pH of about eightwhereupon a colloidal white suspension formed. The hydro-gel wasdecanted, washed with distilled water and filtered. The gel was thenreacidified by mixing one part gel with twenty parts alcohol and asufficient amount of a 20 percent citric acid solution to form acrystalline precipitate of hydrous orthotitanic acid having a pH of 67.The precipitate was filtered from the solution and incorporated into acosmetic vanishing cream base. The sun-screen formulation had thefollowing composition:

The above composition was then tested for ultraviolet absorptionabilities by applying it to the skin of a human subject and exposing thesubject to sunlight 1 hour between 2:00 and 3:00 P.M. The physicalexposure exposure was conducted next to a lake while using a whitebackground. The results 24 hours after exposure indicated that thesun-screen was 100 percent in preventing sunburn.

EXAMPLE 4 This example illustrates the preparation of the preferredchelated form and the sun-screening abilities thereof.

One hundred ml. of tetraispropyl titanate were mixed with 50 ml. oftriethanolamine at 75C to form a chelated triethanolamine titanateproduct. To this product was added, slowly, l00 ml. of distilled waterat 75C. The mixture was stirred until a thin, relatively transparent gelformed. The product was than tested for ultra-violet absorption abilityby dissolving the mixture in distilled water at a ratio of 50 parts ofthe gel to 50 parts water. From the following tabulated results, it isapparent that substantially all of the burning wavelengths, as well as aportion of the tanning rays were absorbed:

The PH of the solution was 7.0.

EXAMPLE 5 The gelatinous triethanolamine titanate product of Example 4was incorporated in the following cream composition and tested for itsultra-violet absorption hours after exposure showed the compound to bepercent effective in preventing sunburn.

It will be appreciated that various modifications and changes may bemade to the various compounds, compositions, and processes of theinvention by those skilled in the art, in addition to those set forthabove, without departing from the spirit thereof. For instance,zirconium may be substituted for titanium in the examples given toprovide an effective ultra-violet absorber. Therefore, the invention isto be limited only by the scope of the appended claims.

What is claimed is:

1. A method for protecting human skin against actinic radiation in theultraviolet region of 200N to 400N which comprises applying to the skina composition comprising:

I. a transparent gelatinous compound of the formula:

a. R, and R are independently selected from the group consisting ofhydrogen, alkyl groups having from three to eight carbon atoms,triethanolamine, octylene glycol and acetyl acetone,

b. n is the number one, and

II. a dermatologically acceptable carrier; said compound being presentin the carrier in an effective sun-screening amount to protect the humanskin from the burning wave lengths of actinic radiation.

2. The method of claim 1 wherein both R and R, are

hydrogen.

3. The method of claim 1 wherein R is isopropyl,

and R, is triethanolamine.

Il ll I0 II

2. The method of claim 1 wherein both R1 and R2 are hydrogen.
 3. Themethod of claim 1 wherein R1 is isopropyl, and R2 is triethanolamine.